ILC2 transfers to apolipoprotein E deficient mice reduce the lipid content of atherosclerotic lesions

Polyxeni T Mantani, Pontus Dunér, Irena Ljungcrantz, Jan Nilsson, Harry Björkbacka, Gunilla Nordin Fredrikson

Research output: Contribution to journalArticlepeer-review

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Abstract

BACKGROUND: Expansion of type 2 innate lymphoid cells (ILC2s) in hypercholesterolaemic mice protects against atherosclerosis while different ILC2 subsets have been described (natural, inflammatory) based on their suppression of tumorigenicity 2 (ST2) and killer-cell lectin like receptor G1 (KLRG1) expression. The aim of the current study is to characterize the interleukin 25 (IL25)-induced splenic ILC2 population (Lin-CD45+IL17RB+ICOS+IL7raintermediate) and address its direct role in experimental atherosclerosis by its adoptive transfer to hypercholesterolaemic apolipoprotein E deficient (apoE-/-) mice.

RESULTS: Immunomagnetically enriched, FACS-sorted ILC2s from the spleens of IL-25 treated apoE-/- mice were stained for KLRG1 and ST2 directly upon cell obtainment or in vitro cell expansion for flow cytometric analysis. IL25-induced splenic ILC2s express high levels of both KLRG1 and ST2. However, both markers are downregulated upon in vitro cell expansion. In vitro expanded splenic ILC2s were intraperitoneally transferred to apoE-/- recipients on high fat diet. ApoE-/- mice that received in vitro expanded splenic ILC2s had decreased lipid content in subvalvular heart and brachiocephalic artery (BCA) plaques accompanied by increased peritoneal B1 cells, activated eosinophils and alternatively activated macrophages (AAMs) as well as anti-phosphorylcholine (PC) immunoglobulin (Ig) M in plasma.

CONCLUSIONS: With the current data we designate the IL25-induced ILC2 population to decrease the lipid content of atherosclerotic lesions in apoE-/- mice and we directly link the induction of B1 cells and the atheroprotective anti-PC IgM antibodies with ILC2s.

Original languageEnglish
Article number47
JournalBMC Immunology
Volume20
DOIs
Publication statusPublished - 2019 Dec 10

Subject classification (UKÄ)

  • Immunology in the medical area

Keywords

  • Adoptive Transfer
  • Animals
  • Apolipoproteins E/deficiency
  • Atherosclerosis/etiology
  • Biomarkers
  • Cytokines/metabolism
  • Disease Models, Animal
  • Immunity, Innate
  • Immunophenotyping
  • Lipids/blood
  • Lymphocytes/immunology
  • Mice
  • Mice, Knockout

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